The goal of the proposed studies is to develop a profile of characteristics associated with invasive human tumor cells. Central to the proposal is the use of an amnion invasion system which will separate tumor cells having a propensity for invasiveness from heterogeneous parent populations of established human colonic adenocarcinomas. The availability of enriched populations of invasive cells will permit study of parameters, associated with these more malignant cells, which might be otherwise masked or subdued within the context of the heterogeneous population. Although the process of tumor cell invasion is key to the whole phenomenon of metastasis, little is known about the characteristics of those human tumor cells that are invasive. For cells to penetrate basement membrane, it is believed that they must first adhere to the membrane, degrade the host stroma, and penetrate the tissue under conditions of reduced nutrient and oxygen supply. Thus, the individual characteristics of attachment, basement membrane degradation, and resistance to hypoxic conditions common to those cells capable to the accumulated act of invasion through the basement membrane will be evaluated. Considered together, these properties may more adequately describe this important component of the metastatic process. It is anticipated that development of this as a model system, and the information derived, will provide insight into new approaches for the study and development of therapy for invasive human carcinoma. (O)